rs551596759

Variant names:

• chr21-32453386-C-T
• rs551596759
• NM_058187.5:c.235C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-32453386-C-T
• chr21-32453386-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001320745.2(EVA1C):​c.-51C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,611,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: EVA1C NM_001320745.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09
• Publications: 0 publications found

Genes affected

EVA1C (HGNC:13239): (eva-1 homolog C) Enables heparin binding activity. Colocalizes with extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

CFAP298-TCP10L (HGNC:54636): (CFAP298-TCP10L readthrough) This locus represents naturally occurring readthrough transcription between the neighboring chromosome 21 open reading frame 59 (C21orf59) and TCP10L (t-complex 10 like) genes on chromosome 21. Readthrough transcripts may encode a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16950399).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320745.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVA1C	NM_058187.5	MANE Select	c.235C>T	p.Arg79Trp	missense	Exon 2 of 8	NP_478067.2
	EVA1C	NM_001320745.2		c.-51C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001307674.1	B3KWG0
	EVA1C	NM_001286556.2		c.235C>T	p.Arg79Trp	missense	Exon 2 of 8	NP_001273485.1	P58658-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVA1C	ENST00000300255.7	TSL:1 MANE Select	c.235C>T	p.Arg79Trp	missense	Exon 2 of 8	ENSP00000300255.2	P58658-1
	EVA1C	ENST00000382699.7	TSL:1	c.235C>T	p.Arg79Trp	missense	Exon 2 of 8	ENSP00000372146.3	P58658-3
	EVA1C	ENST00000437338.5	TSL:1	n.161-4211C>T		intron	N/A	ENSP00000389291.1	A0A0C4DG64

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000797 AC: 20 AN: 250822 AF XY: 0.0000959

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000514 AC: 75 AN: 1459274 Hom.: 0 Cov.: 30 AF XY: 0.0000579 AC XY: 42 AN XY: 725918

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.0000447 AC: 2 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000546 AC: 47 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111476

Other (OTH) AF: 0.0000665 AC: 4 AN: 60182

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74482

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000123 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.24
Sift	Benign	0.066	T
Sift4G	Benign	0.074	T
Polyphen		0.96	D
Vest4		0.57
MutPred		0.46		Gain of sheet (P = 0.039)
MVP		0.28
MPC		1.0
ClinPred		0.84	D
GERP RS		4.8
Varity_R		0.38
gMVP		0.64
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs551596759; hg19: chr21-33825694;